It is proposed to define by nuclear magnetic resonance (NMR), gas chromatographic-nitrogen detection (GC-N) and gas chromatographic-mass spectrometric techniques the actions of lithium carbonate therapy in vivo on various blood cellular elements of psychiatric patients. This is an interdisciplinary project involving pharmacology, psychiatry, and chemistry. The first experiments will study the red blood cells (erythrocytes) of psychiatric patients who are on chronic lithium medication. From preliminary experiments which have already been done using NMR techniques, we have shown in confirmation of the literature, that red cell choline is enormously increased (about 1000%) by lithium. However, a number of additional resonance peaks are also enhanced in the red blood cells of lithium treated patients. The purpose of this grant proposal is to define what these substances are in order to get a complete picture of lithium action. The next step will be to correlate these effects of lithium in the blood of selected psychiatric patients over time, beginning before lithium, and then after lithium therapy for months to years. In addition, these effects on the red blood cell will be correlated with the patients' psychiatric status as a function of duration and dosage of lithium treatment. Finally, this study will be extended to other formed elements of the blood including young vs old blood cells, white cells and platelets. This study stresses the use of NMR techniques to study intact blood cells to measure a large variety of intracellular constituents and will correlate these effects with psychiatric disease state and therapeutic benefit. The working hypothesis of this study is that peripheral blood elements are very convenient, easily available cell systems that can serve as biologic and pharmacologic markers of lithium effects, both therapeutic and toxic.